Şahika Zeynep Akı

Factors affecting stem cell mobilization for autologous hematopoietic stem cell transplantation.

High‐dose chemotherapy with autologous stem cell transplantation (ASCT) is curative treatment in various hematologic malignancies. Mobilization and collection of peripheral blood stem cell is the essential part of ASCT. The aim of this study was to evaluate the effectiveness of various mobilization regimens, determine the risk factors associated with mobilization failure (MF). We also investigated whether iron overload, which has an adverse impact on various aspects of HSCT including overall survival had any impact on mobilization kinetics. A total of 118 consecutive patients were included in this study. The rate of MF was 11.8 % with the first mobilization regimen. Frequency of MF was higher in lymphoma (P < 0.001) patients and in those receiving G‐CSF alone (P= 0.01). Peripheral CD34+ cell count (P < 0.001), bone marrow cellularity (P < 0.001), reticulin fibrosis (P < 0.05) were significantly lower whereas serum ferritin levels (P = 0.06) tended to be higher in patients with MF. CD34+ cell count of the first apheresis product was positively correlated with the white blood cell count (P < 0.05; r = 0.232), platelet count (P = 0.01; r = 0.233), peripheral CD34+ cell count (P < 0.001; r = 0.704) and the grade of bone marrow reticulin fibrosis (P < 0.001; r = 0.366). Serum ferritin levels were negatively correlated with maximum peripheral CD34+ cell count (P = 0.02; r = −0.216) and the CD34+ cell count in the first product (P = 0.05; r = −0.183). Platelet count (P = 0.03; β = 0.262), peripheral CD34+ cell count (P = 0.02; β=0.279) were the two variables which remained to be significant in multivariate analysis. Predicting the poor mobilizers with the platelet count for instance may reduce the risk of MF by using more effective regimens in advance. J. Clin. Apheresis, 2010.

Iron Overload: Predictor of Adverse Outcome in Hematopoietic Stem Cell Transplantation

INTRODUCTION Iron overload is an important problem in candidates for and survivors of hematopoietic stem cell transplantation (HSCT), and affects long-term outcome and survival. The objective of the present study was to determine the effect of iron overload on early toxic or infectious complications and survival. PATIENTS AND METHODS We retrospectively reviewed the medical records for 250 adult patients (162 men and 88 women; median [range] age, 34 [16-71] years who underwent HSCT between September 2003 and August 2008. The HSCT grafts were autologous in 102 patients, and allogeneic in 148. RESULTS Follow-up was 315 (1-1809) days. Mean (SD) pre-HSCT serum ferritin concentration was 1402.6 (5016.2) ng/mL in the entire group, 647.6 (1204.3 ng/mL in autologous recipients, and 1410.6 (2410.4) ng/mL in allogeneic recipients. Twenty-eight autologous graft recipients (27.4%) and 102 allogeneic recipients (68.9%) demonstrated serum ferritin concentrations of 500 ng/mL or greater, and were classified as the high-ferritin group. High ferritin concentrations were significantly associated with toxic or infectious complications including mucositis, fungal infections, pneumonia, and sinusoidal obstruction syndrome in the early post-HSCT setting. A significant effect of pre-HSCT ferritin concentration on overall survival and transplant-related mortality was observed. The effect of pre-HSCT ferritin on survival was independent of the comorbidity index at Cox regression analysis. In the entire study population, the probability of survival was significantly lower when ferritin concentration was greater than 500 ng/mL. CONCLUSION Transplant-related mortality has decreased substantially with the development of supportive treatments. Pretransplantation risk assessment and risk-adapted strategies such as decreasing iron overload might further improve transplant-related complications.

The role of body mass index and other body composition parameters in early post-transplant complications in patients undergoing allogeneic stem cell transplantation with busulfan-cyclophosphamide conditioning

Patients with impaired nutritional status may show increased risk of hematopoietic stem cell transplantation (HSCT)-related complications. This study was conducted to determine whether body mass index (BMI) and other body composition parameters, such as lean body mass index (LBMI) and body fat mass (BFM), are associated with early post-transplantation toxicity and mortality in allogeneic HSCT recipients. The records of 71 patients diagnosed with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), or myelodysplastic leukemia (MDS) who had undergone allogeneic HSCT with a conditioning regimen of busulfan–cyclophosphamide (Bu–Cy), between September 2003 and January 2009 at the Stem Cell Transplantation Unit of Gazi University Hospital were retrospectively evaluated. BMI was found to be negatively correlated with the NCI grade of mucositis, cardiotoxicity, emesis, and hyperglycemia, and with the number of erythrocyte transfusions. LBMI was also negatively correlated with the number of erythrocyte transfusions, cardiotoxicity, emesis, and hyperglycemia. BFM was negatively correlated with the day of neutrophil engraftment, and NCI grade of mucositis. Nutritional status did not have an impact on overall survival (OS), progression-free survival (PFS), or 100-day transplant related mortality (TRM).

Donor lymphocyte infusion for leukemia relapse after hematopoietic stem cell transplantation

Leukemia relapse is a serious therapeutic challenge following hematopoietic stem cell transplantation (HSCT). In this retrospective study, 23 patients [15 (65.2%) AML, 8 (34.8%) ALL] who received DLI+/-reinduction chemotherapy for post-transplant relapse were reviewed. The overall response rate of DLI was 66.7% for AML and 50% for ALL. A total of 15 patients (65.2%) developed acute graft versus host disease (GVHD). Response rates were higher in patients with GVHD (80% versus 25%; p=0.01; OR: 12.0). The probability of OS was better in patients who respond to DLI (p=0.04). Further strategies are required to improve the anti-tumor properties of alloreactive donor lymphocytes and to obtain durable responses with DLI in patients with relapsed acute leukemia after allogeneic HSCT.

Prognostic role of pre‐transplantation serum C‐reactive protein levels in patients with acute leukemia undergoing myeloablative allogeneic stem cell transplantation

The aim of this study was to identify indicators of outcome prior to transplantation in allogeneic hematopoietic stem cell transplantation (HCT). Clinical data of 106 patients with acute leukemia were retrospectively analyzed. We examined the role of pre‐conditioning serum C‐reactive protein (CRP) and ferritin levels, HCT‐CI and European Group for Blood and Marrow Transplantation (EBMT) scores on transplant toxicities, transplant‐related mortality (TRM), progression‐free survival (PFS), and overall survival (OS). High pre‐conditioning serum CRP levels showed a positive correlation with higher EBMT scores (p < 0.001), HCT‐CI (p = 0.004), and ferritin levels (p < 0.001). In univariate Cox regression analysis, serum CRP ≥10 mg/L, serum ferritin ≥1500 ng/mL, and HCT‐CI ≥3 had a significant adverse effect on OS. Serum CRP ≥10 mg/L and HCT‐CI ≥3 predicted increased risk of TRM in univariate analysis. Multivariate Cox regression analysis showed that HCT‐CI score ≥3 independently predicted increased risk of TRM and CRP ≥10 mg/L predicted increased risk of disease progression. Although CRP lost its significance on TRM in multivariate analysis, as an inexpensive and readily available serum biomarker of inflammation, the prognostic role of pre‐transplant CRP levels should be analyzed in selected diseases and increased number of patient groups.

Pro-oxidative/antioxidative imbalance: a key indicator of adverse outcome in hematopoietic stem cell transplantation.

Introduction:  Pretransplantation iron overload (IO) is considered as a predictor of adverse outcome in hematopoietic stem cell transplantation (HSCT). Peroxidative tissue injury caused by IO leads to progressive organ dysfunction.

High ferritin levels are associated with hepatosplenic candidiasis in hematopoietic stem cell transplant candidates

OBJECTIVES Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. METHODS The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. RESULTS HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC. CONCLUSIONS This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients.

Plerixafor use in patients with previous mobilization failure: A multicenter experience

Plerixafor in conjunction with G-CSF (G-P) is an effective strategy for hematopoietic stem cell mobilization in patients with previously failed mobilization attempt. Here we report our results with G-P among patients with at least one mobilization failure with G-CSF alone (G) or G-CSF plus chemotherapy (G-C). The study included 20 consecutive patients with lymphoma and myeloma from five centers. In 14 (70%) patients, a minimum of 2×10(6)/kg CD34+ stem cells were collected and 16 out of 20 patients (80%) were able to proceed to ASCT. Our study indicates that plerixafor can safely rescue patients with a history of mobilization failure.

Prognostic value of bone marrow microvessel density and angiogenic cytokines in patients with multiple myeloma undergoing autologous stem cell transplant

Angiogenesis is important for the proliferation and metastasis of most malignant neoplasms including multiple myeloma (MM). The aim of this study was to evaluate the role of bone marrow angiogenesis and angiogenic cytokines in patients with MM prior to and after autologous stem cell transplant (ASCT). Twenty-nine patients with MM who underwent ASCT had serial samples of serum and bone marrow biopsies at diagnosis, prior to ASCT, and at the 3rd and 6th months post-transplant. Besides bone marrow microvessel density (MVD), serum angiogenic cytokines including vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and markers of disease activity such as interleukin-6 (IL-6), IL-1β, C-reactive protein (CRP), β2-microglobulin, and bone marrow plasma cells (BMPCs) were also determined. Bone marrow MVD, serum levels of IL-6, CRP, and β2-microglobulin, and BMPCs decreased significantly from diagnosis to the 6th month post-transplant (p < 0.05). Serum FGF and IL-1β levels decreased significantly until 3 months post-transplant, however lost this significance at the 6th month. Serum VEGF levels did not vary significantly during follow-up. MVD, serum angiogenic cytokine levels, and parameters reflecting disease activity were similar in responders and non-responders to induction chemotherapy. Cytokines and MVD both at diagnosis and prior to transplant did not show any correlation with overall survival (OS) and progression-free survival (PFS) after a median follow-up of 55 months after transplant (p > 0.05). Our findings suggest that bone marrow MVD decreases significantly with ASCT in MM, however without an impact on OS and PFS.

Allogeneic stem cell transplantation for severe aplastic anemia: Graft rejection remains a problem

We reviewed the outcome in 15 consecutive patients with severe aplastic anemia with a median age of 23 years who received matched sibling peripheral blood stem cell transplantation. Conditioning regimen was cyclophosphamide (Cy)+anti-thymocyte globulin (ATG). Cumulative incidence of transplant related mortality, graft failure, acute and chronic GVHD were 20%, 33%, 25%, and 8.3%, respectively. Conditioning with Cy only, resulted in higher rejection rate compared to Cy plus ATG (75% versus 12.5%, p=0.03). Eighty percent of patients are alive with a median follow-up of 19.5 (4.6-35.6) months. Two of the three patients who were re-transplanted with fludarabine had sustained donor chimerism.